Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis

NCT01731561 | Completed Phase 3

• 2 other identifiers: P1101462012-001963-66
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus systematic infusions.

Conditions

Granulomatosis With Polyangiitis; Microscopic Polyangiitis; Renal Limited Forms

Keywords

Granulomatosis with Polyangiitis; Microscopic polyangiitis; Renal limited forms; ANCA-associated vasculitis; Rituximab

Outcome Measures

Primary Outcomes (1)

• Number of relapses

  Number of relapses (BVAS\>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)

  at 28 months

Secondary Outcomes (13)

• Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies)

  at 28 months

• Number of adverse events

  at 28 months

• Mortality rate

  at 28 months

• Number of minor relapse

  at 28 months

• Cumulated dose of corticosteroid treatment

  at 28 months

Study Arms (2)

Rituximab infusion according biological parameters

EXPERIMENTAL

Rituximab infusion based on ANCA and CD19 lymphocytes

Drug: Rituximab (Arm B)

Systematic rituximab infusion

ACTIVE COMPARATOR

Semestrial rituximab infusion until 18 months

Drug: Rituximab (Arm A)

Interventions

Rituximab (Arm B) DRUG

Rituximab infusion will be performed at D1 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are \> to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.

Rituximab infusion according biological parameters

Rituximab (Arm A) DRUG

Rituximab infusion will be performed at D1, D15, M6, M12 and M18(i.e. a total of 5 infusions), at the dose of 500 mg at a fixed dosage.All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.

Systematic rituximab infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Granulomatosis with Polyangiitis Or microscopic polyangiitis complying Or kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at the time of diagnosis or relapse, and at remission.
• Who have achieved remission using a treatment combining corticosteroids and an immunosuppressive agent, including corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is allowed, according to the current French guidelines, as well as plasma exchanges and/or IV immunoglobulins, or rituximab).
• Interval of 1 month between the end of the immunosuppressant treatment and the randomization time if cyclophosphamide or methotrexate were used, interval between 4 and 6 months if rituximab was used
• Age \> 18 years without age limit higher when the diagnosis is confirmed.
• Informed and having signed the consent form to take part in the study.

You may not qualify if:

• Other systemic vasculitis
• Secondary vasculitis (following neoplastic disease or an infection in particular)
• Induction treatment with a regimen not corresponding to that recommended in France.
• Patient who has not achieved remission.
• Incapacity or refusal to understand or sign the informed consent form.
• Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study. Non-compliance
• Allergy, documented hypersensitivity or contraindication to the study medication (cyclophosphamide, corticosteroids, azathioprine, rituximab)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of contraception throughout the duration of immunosuppressive treatment up to 1 year after the last infusion of rituximab
• Infection by HIV, HCV or HBV
• Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV infection, etc.).
• Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8, HCV, HIV, tuberculosis).
• Progressive cancer or malignant blood disease diagnosed during the 5 years before the diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or those cured of a cancer or a malignant blood disorder for more than 5 years and not taking any antineoplastic agents for more than 5 years may be included.
• Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect.
• No social security

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Cochin Hospital

Paris, 75014, France

Location

Related Publications (2)

• Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A, Hamidou M, Agard C, Bonnotte B, Samson M, Karras A, Jourde-Chiche N, Lifermann F, Gobert P, Hanrotel-Saliou C, Godmer P, Martin-Silva N, Pugnet G, Matignon M, Aumaitre O, Viallard JF, Maurier F, Meaux-Ruault N, Riviere S, Sibilia J, Puechal X, Ravaud P, Mouthon L, Guillevin L; French Vasculitis Study Group. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis. 2018 Aug;77(8):1143-1149. doi: 10.1136/annrheumdis-2017-212878. Epub 2018 Apr 25.

  PMID: 29695500 BACKGROUND

• Khoudour N, Delestre F, Jabot-Hanin F, Jouinot A, Nectoux J, Letouneur F, Izac B, Vidal M, Guillevin L, Puechal X, Charles P, Terrier B, Blanchet B. Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides During Rituximab Maintenance Therapy. Arthritis Rheumatol. 2023 Nov;75(11):2003-2013. doi: 10.1002/art.42556. Epub 2023 Aug 13.

  PMID: 37134130 DERIVED

Related Links

• Website of the French Vasculitis Study Group

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Loic Guillevin, MD, PhD

  Cochin Hospital, Paris, France

  STUDY CHAIR

• Pierre Charles, MD

  Institut mutualiste, Paris, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: November 22, 2012
• Study Start: November 16, 2012
• Primary Completion: April 5, 2016
• Study Completion: April 5, 2016
• Last Updated: September 5, 2025

Record last verified: 2025-08

Locations

FR (1)